Centers for Disease Control and Prevention

National Center for Emerging and Zoonotic Infectious Diseases

Introduction of Policy Questions for TAK-003

Alfonso Hernandez-Romieu, MD, MPH

ACIP June 22, 2023

Dengue Branch, CDC
We formulated PICO questions based on the 

directness of data and risk-benefit differences.

*Persons aged 17 years were considered in this category but were not included in original immunobridging (18 – 60 years) or 

phase 3 trials (4 – 16 years)

• 4–16 years: 57-month vaccine efficacy from a phase 3 

randomized controlled trial

• 17*–60 years: Non-inferiority of antibody titer ratios postvaccination (2 doses) compared to persons aged 4–16 years 

(i.e., immunobridging)

Result: Developed PICO questions by age-group
We formulated PICO questions based on the 

directness of data and risk-benefit differences.

• No efficacy against hospitalizations for DENV-3 among 

seronegative vaccine recipients compared to placebo (-87.9%; 

95% CI: -573.4, 47.6%).

• Data insufficient to rule out an increased risk among 

seronegative vaccine recipients.

Result: Developed PICO questions by serostatus
Hospitalization for DENV-3 and DENV-4 among 

seronegative* children was low.

Placebo

n=1832

Incidence

density/100

person-years

TAK-003

n=3714

Incidence

density/100

person-years

VE (95% CI)

DENV-1 14 0.17 6 0.03 78.4% (43.9, 91.7%)

DENV-2 23 0.28 0 0.0 100% (NE, NE)

DENV-3 3 0.04 11 0.07 –87.9% (–573.4, 47.6%)

DENV-4 1 0.01 0 0.0 100% (NE, NE)

*Seronegative refers to no serologic evidence of previous dengue infection before vaccination.
We formulated PICO questions based on the 

directness of data and risk-benefit differences.

• No efficacy against hospitalizations for DENV-3 among 

seronegative vaccine recipients compared to placebo (-87.9%; 

95% CI: -573.4, 47.6%).

• Data insufficient to rule out an increased risk among 

seronegative vaccine recipients.

Result: Developed PICO questions by serostatus
PICO questions include persons living in 

dengue endemic areas only.

• Recommendations for travelers to dengue endemic areas will be 

addressed by the work group after the October 2023 ACIP meeting.

• Travelers to endemic areas will require a separate evidence-toRecommendations (EtR) framework including but not limited to:

• public health importance

• benefits and harms

• resource use
PICO Questions

1. Should two doses of TAK-003 be administered routinely to seropositive* 

persons aged 4–16 years living in dengue-endemic areas?

2. Should two doses of TAK-003 be administered routinely to seronegative 

persons aged 4–16 years living in dengue-endemic areas?

3. Should two doses of TAK-003 be administered routinely to seropositive* 

persons aged 17–60 years living in dengue-endemic areas?

4. Should two doses of TAK-003 be administered routinely to seronegative 

persons aged 17–60 years living in dengue-endemic areas?

*Recommendation for seropositive individuals only will require prevaccination screening for previous dengue virus infection.
Seropositive Seronegative

4–16 years

Children/Adolescents

• Vaccine Efficacy (VE)

• Safety

• Cost-effectiveness (CE)

• VE

• Safety

• CE

17–60 years

Adults

• Immunobridging*

• Safety

• CE

• Immunobridging

• Safety

• CE

Data elements used for each policy question

*Immunogenicity in seropositive adults inferred from data in seronegative adults.